CN111386083A

CN111386083A - Local fusion of native leaflets using activated adhesive

Info

Publication number: CN111386083A
Application number: CN201880076523.0A
Authority: CN
Inventors: 曹恒楚; S-H·申; H·K·J·许; K·Y-F·赖
Original assignee: Edwards Lifesciences Corp
Current assignee: Edwards Lifesciences Corp
Priority date: 2017-10-20
Filing date: 2018-10-16
Publication date: 2020-07-07
Also published as: WO2019079252A1; US11806001B2; EP3697318A1; CA3078192A1; US20200237357A1

Abstract

Disclosed herein are delivery devices, kits, systems, methods, etc., for locally fusing leaflets of a tissue valve, such as a native heart valve, using an adhesive. The delivery device may include one or more capture features for capturing separate leaflets, e.g., the anterior and posterior mitral leaflets. The applicator may be configured to apply a biocompatible adhesive between the captured leaflets, and the one or more curing elements may be configured to cure the applied biocompatible adhesive. A kit may include the delivery device described above, and a biocompatible adhesive for use therewith. The method may include positioning the delivery device described above adjacent the anterior and posterior mitral valve leaflets, capturing the mitral valve leaflets between the leaflets of the delivery device, applying a biocompatible adhesive between the captured mitral valve leaflets via an applicator, and curing the applied biocompatible adhesive via an energy element to locally fuse the mitral valve leaflets.

Description

Local fusion of native leaflets using activated adhesive

Cross Reference to Related Applications

Priority of U.S. provisional application 62/575,252 to Cao et al, filed 2017 on 20/10 and entitled "Localized Fusion of native leaves Using Activated Adhesive," which is incorporated herein by reference.

Technical Field

The present invention relates generally to devices, systems, and methods for heart valve repair, including the repair of native leaflets using biocompatible surgical glue and/or adhesives.

Background

There is a need for safe and effective devices, systems, techniques, and methods for correcting valve regurgitation. Percutaneous methods for treating valve regurgitation (e.g., mitral regurgitation, tricuspid regurgitation, etc.) may include deploying clips or other devices to hold the ends of the native leaflets together. The catheter may be advanced into a chamber of the heart and the leaflets may be brought together (draw) and/or held together or in a fixed relationship relative to each other using a clip or other device. If a clip or other device is used, it may be necessary to retain it as an implant within the patient once it is deployed. Furthermore, the introduction of foreign bodies or metallic objects into the heart system may create a risk of tissue damage due to mechanical clamping, device displacement, or other damage to surrounding structures.

Disclosure of Invention

This summary is intended to provide some examples, and is not intended to limit the scope of the invention in any way. For example, any feature included in an example of this summary is not required by the claims, unless the claims expressly state such feature. Furthermore, the described features may be combined in various ways. The description herein relates to systems, assemblies, methods, devices, apparatuses, combinations, kits, techniques, etc. for locally fusing valve leaflets (e.g., mitral, tricuspid, aortic and/or pulmonary valve leaflets) using adhesives to restore or improve valve function. Advantageously, the need for permanent implants (e.g., metal devices, clips, spacers, etc.) may be eliminated in many cases. Various features and steps described elsewhere in this disclosure may be included in the examples summarized here.

A delivery device or system for applying an adhesive between valve leaflets (e.g., first and second leaflets; anterior and posterior leaflets; first, second, and third leaflets; etc.) of a tissue valve (e.g., a valve including tissue leaflets, a native heart valve, etc.) for local fusion of the valve leaflets can be provided.

The delivery device or system can include a capture part or parts or capture tools for individually and/or collectively capturing valve leaflets (e.g., first and second leaflets; anterior and posterior leaflets of a mitral valve; first, second, and third leaflets; etc.). These one or more other capture features and/or other features/components described elsewhere in this disclosure may also or alternatively be used or included.

Optionally, the capture feature(s) may include one or more blades (e.g., a pair of opposing blades, three blades, more blades, etc.). The leaflets can be configured such that each leaflet can be hinged individually and/or together between an open configuration and a closed configuration to capture a leaflet (e.g., one or more of an anterior leaflet, a posterior leaflet, a first leaflet, a second leaflet, a third leaflet, etc.).

Optionally, the capture feature(s) can include one or more clips (e.g., a pair of clips, at least four manipulatable clips, more clips, etc.). The clip or a subset of the clips (e.g., at least two clips) may be configured to capture a first leaflet (e.g., the anterior mitral leaflet), the clip or another subset of the clips (e.g., at least two other clips) may be configured to capture a second leaflet (e.g., the posterior mitral leaflet), and/or the clip or another subset of the clips may be configured to capture another leaflet.

The delivery device or system can include an applicator configured to apply adhesive between the leaflets (e.g., between the first leaflet and the second leaflet; between the anterior leaflet and the posterior leaflet of the mitral valve; between the first leaflet, the second leaflet, and the third leaflet; etc.). One or more other applicators, adhesives, and/or other parts/components of these described elsewhere in this disclosure may also or alternatively be used or included. For example, the applicator may optionally include a porous material through which the adhesive is applied. Further, the applicator may be detachable from the capsule, the applicator may be configured to retract within the lumen of the capsule, or both.

The adhesive may be biocompatible. The binder may be one of the binders listed in the present disclosure or have the features/characteristics listed in the present disclosure. In some embodiments, the adhesive comprises at least one prepolymer and at least one initiator. Optionally, at least one prepolymer may be activated by one or more functional groups that may react to form crosslinks between polymer chains. The at least one prepolymer may be composed or selected such that it is not activated by biological fluids. In some embodiments, at least one initiator may be a photoinitiator.

The delivery device or system may also include one or more curing elements or captured anterior and posterior mitral leaflets, and one or more energy elements configured to cure the applied adhesive. The curing element may be configured to deliver Ultraviolet (UV) radiation or other energy to cure the applied adhesive. In one embodiment, at least one of the one or more energy elements is an optical fiber configured to deliver Ultraviolet (UV) radiation out of its distal tip.

In one embodiment, a delivery device for applying adhesive between an anterior mitral valve leaflet and a posterior mitral valve leaflet for local fusion thereof includes one or more capture features for capturing the anterior mitral valve leaflet and the posterior mitral valve leaflet, an applicator configured to apply adhesive between the captured anterior mitral valve leaflet and the posterior mitral valve leaflet, and one or more energy elements configured to cure the applied adhesive. At least one of the one or more energy elements may be configured to deliver Ultraviolet (UV) radiation to cure the applied adhesive. In one embodiment, at least one of the one or more energy elements is an optical fiber configured to deliver Ultraviolet (UV) radiation out of its distal tip. The adhesive may be biocompatible.

In one embodiment, the applicator includes a porous material through which the adhesive is applied.

In one embodiment, the adhesive comprises at least one prepolymer and at least one initiator. Wherein the adhesive comprises at least one prepolymer, the at least one prepolymer being activatable by one or more functional groups, the one or more functional groups being reactive to form crosslinks between polymer chains, and wherein the at least one prepolymer is not activated by the biological fluid. The at least one initiator may be a photoinitiator.

In one embodiment, the one or more capture features include a pair of opposing leaflets, each leaflet configured to articulate between an open configuration and a closed configuration to capture one of an anterior leaflet of the mitral valve or a posterior leaflet of the mitral valve. In one embodiment, the one or more capture features comprise an inflatable balloon, wherein the inflatable balloon captures one of the anterior mitral leaflet or the posterior mitral leaflet. In one embodiment, the one or more capture features comprise at least four manipulable clips, wherein at least two clips are configured to capture an anterior leaflet of the mitral valve and at least two clips are configured to capture a posterior leaflet of the mitral valve.

In one embodiment, the delivery device further comprises a capsule comprising a first end, a second end, and sides extending therebetween, wherein the applicator and the one or more energy elements are connected to the first end of the capsule. The one or more energy elements may be spaced around or substantially around the applicator or at equally spaced locations around the applicator, e.g. such that adjacent energy elements are equidistant from each other and/or from the applicator.

In one embodiment, the applicator is detachable from the capsule. In one embodiment, the applicator is configured to retract within the interior cavity of the capsule.

In one embodiment, the capsule comprises at least one lumen in fluid communication with the applicator, wherein the adhesive is stored in the at least one lumen prior to application between the anterior and posterior mitral leaflets via the applicator.

In one embodiment, the delivery device further comprises an arm connected to the second end of the capsule. Wherein the delivery device comprises an arm, the delivery device may further comprise an expandable scaffold attached to at least a portion of the capsule or at least a portion of the arm, wherein the expandable scaffold is configured to stabilize the delivery device during application of the adhesive between the anterior mitral leaflet and the posterior mitral leaflet.

In one embodiment, the one or more capture features comprise a pair of opposing leaflets attached to at least a portion of the capsule, wherein each leaflet is configured to articulate between an open configuration and a closed configuration to capture one of an anterior leaflet of the mitral valve or a posterior leaflet of the mitral valve.

In one embodiment, a method for locally fusing an anterior mitral leaflet and a posterior mitral leaflet via application of a biocompatible adhesive therebetween includes one, some, or all of: the method includes positioning a delivery device adjacent to the anterior and posterior mitral leaflets of the patient (which may be the same as or similar to the delivery device described above or elsewhere herein), capturing the anterior and posterior leaflets via one or more capture features of the delivery device, applying a biocompatible adhesive between the captured anterior and posterior mitral leaflets via an applicator of the delivery device, and curing the applied biocompatible adhesive via one or more energy elements of the delivery device to partially fuse the anterior and posterior mitral leaflets together. Other steps described elsewhere herein may also be used.

In one embodiment, a delivery device for applying an adhesive between native leaflets for local fusion thereof includes a capture feature for capturing the native leaflets, an applicator configured to apply the adhesive between each native leaflet when captured by the capture feature, and one or more curing elements configured to cure the adhesive after application to the native leaflets. At least one of the one or more curing elements may be configured to deliver Ultraviolet (UV) radiation to cure the adhesive. At least one of the one or more curing elements may be an optical fiber configured to deliver Ultraviolet (UV) radiation out of its distal tip. The adhesive may be biocompatible.

In one embodiment, the adhesive comprises at least one prepolymer and at least one initiator. In one embodiment, wherein the adhesive comprises at least one prepolymer, the at least one prepolymer may be activated by one or more functional groups that may react to form crosslinks between polymer chains, and wherein the at least one prepolymer is not activated by a biological fluid. In one embodiment, wherein the adhesive includes at least one initiator, the at least one initiator may be a photoinitiator.

In one embodiment, the capture feature comprises opposing leaves, each leaf configured to hinge between an open configuration and a closed configuration to capture one of the native leaflets. In one embodiment, the one or more capture features comprise an inflatable balloon, wherein the inflatable balloon captures one of the native leaflets.

In one embodiment, the capture feature comprises at least four manipulable clips, wherein at least two clips are configured to capture a first native leaflet and at least two clips are configured to capture a second native leaflet.

In one embodiment, the delivery device further comprises a capsule comprising a first end, a second end, and sides extending therebetween, wherein the applicator and the one or more curing elements are connected to the first end of the capsule. The capsule may include one or more lumens in fluid communication with the applicator, wherein the adhesive is stored in the one or more lumens prior to application between the native leaflets via the applicator.

In one embodiment, the delivery device further comprises an arm connected to the second end of the capsule. Wherein the delivery device comprises an arm, the delivery device may further comprise an expandable stent connected to at least a portion of the capsule or at least a portion of the arm. The expandable stent can be configured to stabilize the delivery device during application of the adhesive between the native leaflets.

In one embodiment, the applicator is detachable from the capsule or another part or component of the delivery system. In one embodiment, the applicator is configured to retract within the lumen of the capsule or the lumen of another part or component of the delivery system.

Wherein the delivery device comprises a capsule, the catch feature may comprise opposing blades attached to at least a portion of the capsule. Each leaflet may be configured to articulate between an open configuration and a closed configuration simultaneously or individually to capture each native leaflet.

The capture feature may comprise a balloon, wherein the balloon is inflatable to capture one of the native leaflets.

In one embodiment, the capture feature comprises at least four manipulable clips, wherein at least two clips are configured to capture the first leaflet and at least two clips are configured to capture the second native leaflet.

In one embodiment, the one or more curing elements substantially surround the applicator. The one or more curing elements may be arranged in an equidistant arrangement around the applicator and each may be equidistant from the applicator. Each pair of adjacent curing elements may be equidistant from each other around the applicator.

In one embodiment, the method for locally fusing natural leaflets via application of an adhesive therebetween comprises one, some or all of: the method includes positioning a delivery device (which may be the same or similar to the delivery devices described above or elsewhere herein) adjacent the native leaflets of the patient, capturing the native leaflets via a capture feature of the delivery device, applying an adhesive between the native leaflets via an applicator of the delivery device after capturing the native leaflets, and curing the adhesive via one or more curing elements of the delivery device to partially fuse the native leaflets together. Other steps described elsewhere herein may also be used.

In one embodiment, a delivery device for applying adhesive between a native mitral valve anterior leaflet and a native mitral valve posterior leaflet for local fusion thereof includes a capture tool for capturing the anterior leaflet and the posterior leaflet, an applicator configured to apply adhesive between the anterior leaflet and the posterior leaflet once captured by the capture tool, and at least one curing element configured to cure the adhesive after application between the anterior leaflet and the posterior leaflet. The at least one curing element may be configured to deliver Ultraviolet (UV) radiation to cure the adhesive.

The adhesive may include at least one prepolymer and at least one initiator. Wherein the adhesive comprises at least one prepolymer, the at least one prepolymer being activatable by one or more functional groups which can react to form crosslinks between polymer chains. In various embodiments, the at least one prepolymer is not activated by a biological fluid. The at least one initiator may be one photoinitiator or a plurality of photoinitiators.

In one embodiment, the capture tool comprises a pair of opposed blades. Each leaf may be configured to articulate between an open configuration and a closed configuration to capture one of the anterior or posterior leaflets, respectively.

In one embodiment, the capture tool includes a pair of balloons. Each balloon of the pair of balloons may be configured to capture one of the anterior mitral leaflet or the posterior mitral leaflet, respectively, when the balloon is inflated.

In one embodiment, the capture tool comprises a plurality of clips. At least two of the plurality of clips may be configured to capture the anterior leaflet and at least two of the plurality of clips may be configured to capture the posterior leaflet.

In one embodiment, the delivery device further comprises a capsule comprising a first end, a second end, and sides extending therebetween. The applicator and the at least one curing element may be connected to a first end of the capsule.

In one embodiment, the applicator is detachable from the other components of the delivery device. In one embodiment, the applicator is retractable within another component of the device.

In one embodiment, the delivery device comprises an expandable stent. The expandable scaffold may be configured to stabilize the delivery device during application of adhesive between the anterior and posterior leaflets.

In one embodiment, a method for locally fusing the anterior leaflet and the posterior leaflet of a mitral valve via applying an adhesive therebetween includes positioning a delivery device (which may be the same as or similar to the delivery devices described above or elsewhere herein) adjacent the anterior leaflet and the posterior leaflet of the mitral valve, capturing the anterior leaflet and the posterior leaflet, respectively, of the mitral valve via a capture tool of the delivery device, applying the adhesive between the anterior leaflet and the posterior leaflet via an applicator of the delivery device, and after applying the adhesive, curing the adhesive via at least one curing element of the delivery device to locally fuse the anterior leaflet and the posterior leaflet together. Other steps described elsewhere herein may also be used.

In one embodiment, a delivery device for applying an adhesive between leaflets of a tissue valve for local fusion thereof includes a capture tool for capturing at least a first leaflet and a second leaflet of the tissue valve, an applicator configured to apply the adhesive between the at least first leaflet and the second leaflet once captured by the capture tool, and at least one energy element configured to cure the adhesive after the adhesive is applied between the at least first leaflet and the second leaflet. The at least one energy element or the plurality of energy elements may be configured to deliver Ultraviolet (UV) radiation to cure the adhesive.

In one embodiment, the adhesive comprises at least one prepolymer and at least one initiator. At least one prepolymer may be activated by one or more functional groups that may react to form crosslinks between polymer chains. In one embodiment, the at least one prepolymer is not activated by biological fluids. The at least one initiator may be one photoinitiator or a plurality of photoinitiators.

In one embodiment, the capture tool comprises a pair of opposed blades. Each leaflet may be configured to articulate between an open configuration and a closed configuration to capture a first leaflet or a second leaflet, respectively.

In one embodiment, the capture tool includes a pair of balloons. Each balloon may be configured to inflate to capture one of the first leaflet or the second leaflet.

In one embodiment, the capture tool comprises a plurality of clips. At least two clips of the plurality of clips may be configured to capture a first leaflet and at least two clips of the plurality of clips may be configured to capture a second leaflet.

In one embodiment, the delivery device further comprises a capsule comprising a first end, a second end, and sides extending therebetween. The applicator and the at least one energy element may be connected to a first end of the capsule.

In one embodiment, the applicator is detachable from other components of the delivery device, such as the capsule, etc. In one embodiment, the applicator is configured to be retracted within another component of the delivery device, such as within a sealed capsule or the like.

In one embodiment, the delivery device further comprises an expandable stent. The expandable stent can be configured to stabilize the delivery device during application of the adhesive between at least the first leaflet and the second leaflet.

The above-described devices and systems may include additional components as described elsewhere herein.

In one embodiment, a method for locally fusing leaflets of a tissue or heart valve via application of an adhesive therebetween includes positioning a delivery device (which may be the same as or similar to the delivery devices described above or elsewhere herein) adjacent to at least first and second leaflets of the tissue or heart valve, capturing capture means of the first and second leaflets via the delivery device, respectively, applying the adhesive between the at least first and second leaflets via an applicator of the delivery device, and after applying the adhesive, curing the adhesive via at least one energy element of the delivery device to locally fuse the at least first and second leaflets together. Other steps described elsewhere herein may also be used.

Also described herein are various methods comprising applying an adhesive to leaflets of a tissue valve and various related or additional steps. For example, a method for locally fusing leaflets via application of an adhesive (e.g., a biocompatible adhesive, etc.) therebetween can include positioning a delivery device adjacent leaflets of a valve (tissue valve, heart valve, etc.) (e.g., adjacent anterior and posterior mitral leaflets, etc.). The method can include capturing the leaflets (e.g., capturing the anterior and posterior leaflets, etc.) via the capture feature(s) of the delivery device. The method can include applying an adhesive between the leaflets after capturing the leaflets via an applicator of the delivery device. The method can further include curing the applied adhesive via one or more curing elements or energy elements of the delivery device to locally fuse the leaflets (e.g., anterior and posterior mitral leaflets, etc.) together. Any of the delivery devices or systems described in this disclosure may be used. In addition, any other steps described elsewhere in this disclosure may also be used.

Drawings

Exemplary and non-limiting embodiments of the invention may be more readily understood by referring to the accompanying drawings in which:

fig. 1A-1C and 1D are side and top views, respectively, of an exemplary delivery device (e.g., a left ventricular delivery device) for local fusion of mitral valve leaflets via a biocompatible adhesive, according to one embodiment.

Fig. 2 is a side view of the delivery device of fig. 1A-1D, wherein the applicator is detachable according to one embodiment.

Fig. 3 is a simplified schematic view of a mitral valve leaflet that has been fused via use of the delivery device of fig. 2, wherein the fused mitral valve leaflet includes a separate applicator and an adhesive present therebetween according to one embodiment.

Fig. 4 is a side view of the delivery device of fig. 1A-1D, wherein the applicator thereof is retractable according to one embodiment.

Fig. 5 is a simplified schematic view of a mitral valve leaflet that has been fused via use of the delivery device of fig. 4, wherein the fused mitral valve leaflet includes only a biocompatible adhesive present therebetween according to one embodiment.

Fig. 6 is a side view of the delivery device of fig. 1A-1D with an arm portion thereof connected to an optional handle according to one embodiment.

Fig. 7 is a side view of the delivery device of fig. 1A-1D illustrating one or more lumens/cavities thereof according to one embodiment.

Fig. 8 is a side view of the delivery device of fig. 1A-1D illustrating a delivery sheath to cover and/or protect the delivery device according to one embodiment.

Fig. 9 is a side view of the delivery device of fig. 1A-1D illustrating an exemplary design thereof according to one embodiment.

Fig. 10 is a side view of the delivery device of fig. 1A-1D illustrating an exemplary design thereof according to one embodiment.

Fig. 11 is an elevation view of a pair of exemplary leaflets configured to capture leaflets (e.g., anterior mitral and posterior mitral leaflets), according to one embodiment.

Fig. 12 is a side view of an exemplary delivery device having an inflatable balloon for capturing native valve leaflets, according to one embodiment.

Fig. 13A-13B are side and interior views, respectively, of an exemplary delivery device (e.g., a left atrial delivery device) for local fusion of native leaflets (e.g., mitral valve leaflets) via a biocompatible adhesive, according to one embodiment.

FIG. 14 is a top view (topdown view) of a delivery device illustrating an exemplary 3-blade configuration, according to one embodiment.

Fig. 15A is a side view of an exemplary delivery system including an expandable stent, according to one embodiment.

Fig. 15B is a side view of an exemplary delivery system including an expandable stent, wherein an inflatable balloon is used to expand the stent according to one embodiment.

Fig. 16A-16C illustrate an exemplary method of using a left ventricular delivery device as described herein, according to one embodiment.

Fig. 17 illustrates an exemplary method of using a left atrial delivery device as described herein, according to one embodiment.

Fig. 18A illustrates a mitral valve according to the definition of Carpentier.

Fig. 18B illustrates a top view of a mitral anterior leaflet and a mitral posterior leaflet fused via a biocompatible adhesive, such as may be applied via the devices, systems, and methods described herein.

Detailed Description

The present disclosure provides novel devices, systems, components, parts, methods, etc. for correcting or substantially minimizing valve regurgitation (e.g., mitral regurgitation). For example, the present disclosure provides devices, systems, methods, etc. for correcting or substantially minimizing valve regurgitation (e.g., mitral regurgitation) via the application of a biocompatible adhesive between the native leaflets (e.g., between the anterior and posterior leaflets of the mitral valve). Curing may be performed by exposure to Ultraviolet (UV) radiation, other radiation, heat, or in some other manner. Such biocompatible adhesives may be water-impermeable, blood-resistant, and may adhere to wet tissue (wet tissue). When such a biocompatible adhesive is cured, the leaflets (e.g., mitral valve leaflets, portions thereof, or other leaflets) are joined together. When the mitral valve leaflets are joined, they can form a double-orifice configuration, thereby minimizing or reducing mitral regurgitation without the use of permanent implants, devices, metallic materials, and the like.

If a clip or other mechanical device is used to hold the leaflets together, the mechanical device/clip must remain in the heart system indefinitely. The biocompatible adhesives used in the devices, systems, methods, etc. described herein negate or minimize the risk of tissue damage due to mechanical clamping or device dislodgement. The biocompatible adhesive may be repositioned to minimize mitral regurgitation. However, in contrast to mechanical repositioning and repeated clamping that may be required by clips or other devices, the properties of the biocompatible adhesive may be selectively activated via a curing process (e.g., via exposure to UV radiation) only when the adhesive is positioned on the mitral valve leaflets as needed, thereby minimizing the risk of tissue damage during conditioning.

Further, as disclosed herein, exemplary devices for delivering a biocompatible adhesive may be advanced through the body and to the desired valve in various ways, such as trans septally, transapically, femorally, or the like. Thus, such a delivery device may include a unique capture tool for capturing the anterior or posterior mitral leaflet according to a delivery/delivery route through the heart.

Referring now to fig. 1A-1D, an exemplary delivery device 100 for applying adhesive between leaflets of a native valve is shown. While the delivery device 100 is adapted (adapt) such that it may apply adhesive between the posterior and anterior leaflets of the mitral valve, and may be described herein with reference to the mitral valve, the invention is not so limited and principles, features, etc. may be adapted and applied to other valves. The delivery device 100 may be advanced through the left ventricular cavity of the patient's heart and/or through other chambers of the heart. The delivery device 100 or components/parts thereof may be combined with or alternatively implemented with other devices/parts/components described herein (such as those described with reference to other embodiments and figures). The delivery device 100 may additionally be used in any method for making and/or using such devices/components/parts described herein. The delivery device 100 may also be used in a variety of applications and/or arrangements, which may or may not be indicated in the illustrative embodiments described herein. For example, in some embodiments, the delivery device 100 may include more or fewer parts/components than those shown in fig. 1A-1D. Further, the delivery device 100 is not limited to the size, shape, number, etc. of the components specifically shown in fig. 1A-1D.

As shown in fig. 1A-1D, some embodiments of the delivery device 100 include a capture part 102, a capsule 104, an applicator 106, and an arm 108 to capture leaflets and pull and/or move the leaflets toward each other. As shown in fig. 1A-1D, the capture part 102 can be comprised of blades (e.g., one, two, three, or more blades). Although blades are shown in these figures, the capture features may include other means of pulling and/or moving the leaflets toward one another, such as jaws, clips, arms, extensions, attachment portions, inflatable balloons, and/or combinations thereof. In the example shown in fig. 1A-1D, the capture feature comprises two

leaflets

102a, 102b, each of which includes an

attachment portion

110a, 110b that contacts the capsule 104 and is configured to contact, capture, and move an end (a "free end" portion) 112a, 112b of a mitral leaflet (e.g., anterior mitral leaflet 114a or posterior mitral leaflet 114 b). As discussed in more detail herein, the pair of

leaflets

102a, 102b can be configured to contact and capture the mitral valve leaflet from the outer surface of the native leaflet (e.g., the outer surface of the anterior and posterior

mitral leaflets

114a, 114b or the ventricular surface).

In some embodiments, the catch pieces or leaves 102a, 102B move from an open configuration (e.g., as illustrated in fig. 1A) to a closed configuration (e.g., as illustrated in fig. 1B), and vice versa. In the open configuration (fig. 1A), the

ends

112a, 112b of the catch pieces or leaves 102a, 102b may be separated by a first distance. The first distance corresponds to the maximum distance that the

ends

112a, 112b of the catch parts or

blades

102a, 102b can be separated from each other. In some embodiments, the separation of the

ends

112a, 112b of the capturing parts or

blades

102a, 102b by the first distance may result in the capturing parts or blades having a substantially "pseudo-V" shape or pseudo-conical shape, wherein the first distance is greater than the distance between the

attachment portions

110a, 110 b. In some embodiments, the first distance is sufficient to enable the capture features or

leaflets

102a, 102b to contact and capture the native leaflet (e.g., to capture the anterior and posterior

mitral leaflets

114a, 114 b).

In the closed configuration (fig. 1B), the ends 112a, 112B of the catch pieces or leaves 102a, 102B are closer together, forming a second distance that is less than the first distance described above. The second distance may be a minimum distance that ends 112a, 112b of the catch pieces or

blades

102a, 102b are separated from each other. In some embodiments, the separation of the

ends

112a, 112b of the capturing parts or

blades

102a, 102b by the second distance may result in the ends being in contact with each other, or in close contact with each other (e.g., within 1-3 mm).

In some embodiments, the leaflets 102a, 102B are in an open configuration (fig. 1A) when brought into contact with the native valve leaflets, and then move into a closed configuration (fig. 1B) to simultaneously pull and/or move the native leaflets to apply the adhesive therebetween. For example, the delivery device 100 may be positioned in the left ventricle of the heart with the

leaflets

102a, 102b in the open configuration (fig. 1A). The

ends

112a, 112b are placed in contact with the anterior and posterior

mitral leaflets

114a, 114b to capture the leaflets (this may be done simultaneously or sequentially one leaflet at a time). The leaflets 102a, 102B are then placed in the closed configuration (fig. 1B) to simultaneously pull and/or move the mitral leaflets 114a, 114B to apply the adhesive 118 therebetween.

In situations where the native leaflets (e.g., anterior and

posterior leaflets

114a, 114b) need to be re-adjusted relative to the delivery device 100, the capture features or

leaflets

102a, 102b can be opened and closed until an optimal position and/or coaptation depth is achieved.

In some embodiments, after applying adhesive to one or more portions of the capture leaflets (e.g., 114a, 114b), the capture pieces or

leaflets

102a, 102b can be moved from the closed configuration to the open configuration and removed from the vicinity of the

leaflets

114a, 114b, now sealed via the adhesive. Once the capture features or leaves 102a, 102b are no longer in proximity to the

leaflets

114a, 114b, the capture features or leaves can move back to the closed configuration during withdrawal of the delivery device 100 from the heart (e.g., for a lower profile; such a lower profile can also be used during introduction into the body and heart).

Zero captureMovement and/or rotation of the pieces (e.g.,

blades

102a, 102b) may be accomplished via various mechanical means. For example, each capture part or

leaf

102a, 102b in some embodiments will include at least two different segments oriented at different angles (e.g., as measured along the z-axis in fig. 1A-1D) relative to the longitudinal axis of the delivery system 100. As shown in the embodiments of FIGS. 1A-1D, a capture part or blade 102a may include a first segment 102a₍₁₎And a second segment 102a₍₂₎Wherein the first segment 102a₍₁₎Includes an attachment portion 110a, and a second section 102a₍₂₎Including end 112 a. Likewise, the capture part or vane 102b can include a first segment 102b that includes an attachment portion 110b₍₁₎And a second section 102b including an end 112b₍₂₎. In some embodiments, two sections (e.g., 102 a) of each capture part or blade₍₁₎And 102a₍₂₎) Connected by a joint (fig. 1C, 124a and 124 b). The

joints

124a, 124b may allow for the second section 102a of each capture part or

blade

102a, 102b₍₂₎、102b₍₂₎Relative to the first segment 102a₍₁₎、102b₍₁₎Movement and/or rotation. For example, some embodiments of the

joints

124a, 124b will allow for the second section 102a of each capture part or

blade

102a, 102b₍₂₎、102b₍₂₎Moving in a direction along (or parallel to) the x-axis shown in fig. 1A-1D to transition between an open configuration and a closed configuration. In some embodiments, the

joints

124a, 124b will allow for the second section 102a of each capture part or

blade

102a, 102b₍₂₎、102b₍₂₎Moving in a direction along (or parallel to) the y-axis shown in fig. 1A-1D. In some embodiments, the

joints

124a, 124b will allow for the second section 102a of each capture part or

blade

102a, 102b₍₂₎、102b₍₂₎Rotated a predetermined amount about the z-axis shown in fig. 1A-1D. In some embodiments, the

joints

124a, 124b will allow for the second section 102a of each capture part or

blade

102a, 102b₍₂₎、102b₍₂₎Along a combination of x-axis, y-axis, and/or z-axis as illustrated in fig. 1A-1D. These may be combined in various ways.

In some embodiments, each capture feature (e.g., each

blade

102a, 102b) may be composed of a single, continuous material, which may or may not have one or more differently angled sections. Thus, some embodiments include a joint (fig. 1C, 126a, and 126b) to connect the

attachment portion

110a, 110b of each capture feature or

blade

102a, 102b to a portion of the delivery device 100 to allow movement and/or rotation of the capture feature or

blade

102a, 102 b. For example, the

joints

126a, 126b enable each capture part or

blade

102a, 102b to move in a direction along (or parallel to) the x-axis shown in fig. 1A-1D to transition between an open configuration and a closed configuration; moving in a direction along (or parallel to) the y-axis; and/or a predetermined amount about the z-axis.

In some embodiments, each capture part (e.g., each

blade

102a, 102b) is connected to a portion of the delivery device 100 via a joint (e.g., 126a) to allow movement and rotation of the entire capture part or blade, and further includes at least two segments (e.g., 102 a) connected by another joint (e.g., 124a)₍₁₎And 102a₍₂₎) To allow movement and/or rotation of a particular segment relative to another segment.

In some embodiments, each capturing part or segment thereof is configured to move independently of the other capturing parts or segments thereof. For example, the blade 102a or segment thereof may move independently of the blade 102b or segment thereof. However, in other embodiments, the capturing parts (e.g., the two

blades

102a, 102b) or segments thereof move in unison such that movement of one capturing part or blade or segment thereof causes, and/or is associated with a mirrored movement of the other capturing part or blade or segment thereof.

As shown in the embodiments in fig. 1A-1D, the

attachment portion

110a, 110b of each capture feature or

blade

102a, 102b may be connected to the side of the capsule 104. In one embodiment (such as illustrated in fig. 9), the

attachment portion

110a, 110b of each capture feature or

blade

102a, 102b is connected to an upper surface (first end) 116 of the capsule 104 with the applicator 106 positioned therebetween. In one embodiment, the

attachment portion

110a, 110b of each capture feature (e.g.,

blade

102a, 102b) is connected to a portion of the arm 108. Various attachment points and combinations are possible.

Regardless of the point of attachment to the delivery device 100, each capture feature (e.g., the

leaflets

102a, 102b) can have dimensions suitable for contacting and capturing native leaflets (e.g., the anterior and posterior

mitral leaflets

114a, 114 b). In some embodiments, each capture feature (e.g.,

blade

102a, 102b) can have a length/height (as measured along the z-axis in fig. 1A-1D) in the range of about 2 to about 10 mm; a width (as measured along the y-axis in FIGS. 1A-1D) in the range of about 2 to about 8 mm; and/or a thickness (as measured along the x-axis in fig. 1A-1D) in a range of about 0.2 to about 1 mm.

In some embodiments, each capture feature or

blade

102a, 102b has a uniform or substantially uniform width along its length (e.g., along the z-axis). In other embodiments, each capture feature or

blade

102a, 102b may not have a uniform width along its length. For example, in such other embodiments, each capture feature or

blade

102a, 102b can have a greater width near the end (e.g., 112a, 112b) than the attachment portion (e.g., 110a, 110b) or other portion positioned therebetween. In at least one embodiment, the width of each capture feature or

blade

102a, 102b gradually increases from the attachment portion (e.g., 110a, 110b) to the end (e.g., 112a, 112b) thereof. In other embodiments, the width of each capture feature or

blade

102a, 102b is uniform or substantially uniform along its length, but the width increases abruptly near the ends (e.g., 112a, 112 b).

Some embodiments have capture features (e.g.,

blades

102a, 102b) constructed from a suitable biocompatible material. Exemplary biocompatible materials for the capture parts or

blades

102a, 102b can include, but are not limited to, metal alloys (e.g., Ti alloys such as Ti-6 Al-4V; Co-Cr alloys such as Co-Cr-Mo; nitinol; Au alloys; Ag alloys; etc.), stainless steel, plastic materials, polymeric materials, combinations of these, and the like. In some embodiments, the capturing parts or leaves 102a, 102b are constructed of cloth or foldable woven mesh.

In some embodiments, as shown in fig. 1A-1D, the delivery device 100 includes an applicator 106 protruding from an upper surface (first end) 116 of the capsule 104. Applicator 106 may specifically be configured to position/insert a leaflet of a native valve, such as between the anterior and posterior

mitral leaflets

114a, 114b captured between capture features or

leaflets

102a, 102 b. Further, the applicator 106 may be configured to dispense and/or apply adhesive between captured leaflets, such as the anterior and posterior

mitral leaflets

114a, 114b illustrated in fig. 1A-1C. To this end, the capture features or leaflets 102a, 102B can be moved to a closed configuration (e.g., as shown in fig. 1B) such that the sidewalls of the applicator 106 contact and/or are in close proximity to at least a portion of the captured mitral valve leaflets 114a, 114B, thereby enabling the adhesive 118 to be applied directly to the portion of the leaflets 114a, 114B via the applicator 106. In some embodiments, adhesive 118 may be applied to an intermediate section of mitral valve leaflets 114a, 114B (e.g., the a2-P2 section (see fig. 18A-18B)) via applicator 106.

In some embodiments, the applicator 106 is constructed of a porous and/or permeable material through which the adhesive 118 may be applied and/or dispensed. For example, the porous material may be a woven, braided, and/or sponge-like material. In various embodiments, the porous and/or permeable material is soft and/or compressible, while in other embodiments, the porous and/or permeable material is rigid or partially rigid. The porous and/or permeable material may be biocompatible and/or biodegradable (bioabsorbable). For example, the applicator 106 may comprise a biocompatible and biodegradable (bioabsorbable) polymer sponge or cloth bag. Exemplary materials for the applicator 106 include, but are not limited to, fabric, polymeric materials. Further examples of materials that may be used include, but are not limited to, poly (lactic acid) (PLA), poly (lactic acid-co-glycolic acid), Polycaprolactone (PCL), Polyhydroxybutyrate (PHB), poly (3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV), polypropylene carbonate (PPC), polybutylene succinate (PBS), fumaric acid polyacrylate (PPF), polyurethane polymers, poly (L-lactide) (PLLA), poly (D-lactide) (PDLA), Polyglycolide (PGA), poly (L-lactide-co-glycolide) (PLGA), Polyhydroxyalkanoates (PHA), polysaccharides, proteins, polyesters, polyhydroxyalkanoates, polyalkenoates, polyamides, polycaprolactone, polylactide-co-polycaprolactone, polyvinyl ester, Polyesteramides, polyvinyl alcohols, modified derivatives of caprolactone polymers, polytrimethylene carbonate, polyacrylates, polyethylene glycols, hydrogels, photocurable hydrogels, terminal dial (terminal dial), poly (L-lactide-co-trimethylene carbonate), polyhydroxybutyrate; polyhydroxyvalerate, polyorthoester, polyanhydride, polyimmocarbonates, type I collagen, type III collagen, type IV collagen, type VI collagen, type XI collagen, type XII collagen, type I fibrillin, tenascin, decorin, byglycan, pluripotent proteoglycan, apocrin, and combinations thereof.

In various embodiments, the applicator 106 maintains a shape and/or size suitable to allow and/or maximize the application of the adhesive 118 between the captured leaflets (e.g., anterior and posterior

mitral leaflets

114a, 114 b). In some embodiments, the applicator 106 has a length/height (as measured along the z-axis in fig. 1A-1D) that is the same as (including substantially the same as) the length/height of the capture features or

blades

102a, 102 b. In some embodiments, the applicator 106 has a length/height that is shorter than the length/height of the capturing parts or

blades

102a, 102b, such as illustrated in fig. 1A-1C. For example, the applicator 106 may have a length/height that is about 25% to about 100% of the length/height of the capture features or

blades

102a, 102 b. Additionally, in some embodiments, the applicator 106 has a generally circular shape, such as an ellipse or oval, while other embodiments may have an applicator 106 with a rectangular or other cross-sectional shape. It should be noted that in embodiments where the applicator 106 comprises a soft and/or compressible material, the shape of the applicator 106 can be adjusted to conform to the shape of the adjacent portion of the captured leaflet (e.g., 114a, 114 b).

Suitable adhesives will include one or more (e.g., some or all) of the following features: (1) the adhesive has sufficient viscosity such that it withstands hemodynamics and resists washing away from the application site; (2) the adhesive does not react with and/or crosslink with bodily fluids (e.g., blood) in the presence of the bodily fluids without exposure to at least one external stimulus; (3) the binder is hydrophobic to prevent dilution by aqueous solutions; (4) the adhesive is capable of adhering to wet tissue; (5) the adhesive is biocompatible; and (6) the adhesive is biodegradable.

The biodegradability of the binder may be an advantageous property as it will allow the binder to slowly degrade, thereby limiting the amount of foreign particles in the body. Over time, the permanent and foreign substances remaining in the body may cause injury, disease, inflammation, or other adverse effects. The adhesive may produce a similar reaction in vivo, as the adhesive may detach and migrate elsewhere within the circulatory system, or even cause an immune response in vivo. A solution to prevent possible long-term effects is to use biodegradable adhesives. The biodegradable adhesive can hold the leaflets for a sufficient period of time that the tissue regeneration process will permanently fuse the leaflets. After the leaflets are permanently fused by natural processes, the adhesive will no longer function to secure the leaflets. Likewise, a suitable biodegradable adhesive will firmly secure the leaflets for a sufficient period of time for tissue fusion to occur. After biodegradation, the adhesive, foreign matter, has completely or substantially disappeared and long-term adverse effects will be prevented or limited.

Adhesives suitable for use in combination with the delivery devices described herein may include a crosslinking prepolymer and an initiator. U.S. patent application publication No. 2014/0348896, published on 27/11/2014; us patent No. 9,006,182 granted on day 14/4/2015; lang et al, "A Blood Resistant scientific Glue for minor invasion repair of Vessels and Heart Defects", Sci. Transl. Med., 2014, 6(218), 1-20; and Khadem et al, "health of Forming Rat Corneal associations Closed with Photocurable Glue Laser-Activated Tissue Glue", Laser Surg. Med.2004, 35(4), 304-; the entire contents of which are incorporated herein by reference.

In some embodiments, the adhesive will include one or more prepolymers. The prepolymer(s) may be activated by introducing one or more functional groups (i.e., incorporated onto the prepolymer backbone) that may react to form crosslinks between the polymer chains. The functional group may be selected from: substituted vinyl groups, unsubstituted vinyl groups, substituted acrylate groups, unsubstituted acrylate groups, vinyl esters, vinyl carbamates, ketene, vinyl amides, vinyl carbonates, vinyl ether groups, vinyl groups in allyl form, combinations of these, and the like. In one embodiment, the polymer chain is a polyester formed from a substituted or unsubstituted polyol, such as a triol, which may be glycerol, and a substituted or unsubstituted diacid. The functional group can also form crosslinks with tissue (e.g., native valve or leaflet tissue).

In some embodiments, the prepolymer will be selected based on the degree of activation. For example, the degree of activation may be 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5. The degree of activation of the prepolymer can range between and including any two of the values recited above. The degree of activation of the prepolymer may be one of the following: about 0.001, about 0.002, about 0.003, about 0.004, about 0.005, about 0.006, about 0.007, about 0.008, about 0.009, about 0.01, about 0.02, about 0.03, about 0.04, about 0.05, about 0.06, about 0.07, about 0.08, about 0.09, about 0.1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.1, about 1.2, about 1.3, about 1.4, or about 1.5 ("about" is the lowest decimal place ± 1 of each number listed).

In some embodiments, the prepolymer is selected based on molecular weight, and higher molecular weight prepolymers result in more viscous compositions. For example, the molecular weight can be one of the following values or about/approximately (e.g., ± 500 daltons) one of the following values: 1,000 daltons, 2,000 daltons, 3,000 daltons, 4,000 daltons, 5,000 daltons, 6,000 daltons, 7,000 daltons, 8,000 daltons, 9,000 daltons, 10,000 daltons, 11,000 daltons, 12,000 daltons, 13,000 daltons, 14,000 daltons, 15,000 daltons, 16,000 daltons, 17,000 daltons, 18,000 daltons, 19,000 daltons, 20,000 daltons, 21,000 daltons, 22,000 daltons, 23,000 daltons, 24,000 daltons, 25,000 daltons, 26,000 daltons, 27,000 daltons, 28,000 daltons, 29,000 daltons, 30,000 daltons, 35,000 daltons, 40,000 daltons, 45,000 daltons, 50,000 daltons, 55,000 daltons, 60,000 daltons, 65,000 daltons, 70,000 daltons, 80,000 daltons, or more. The molecular weight of the prepolymer can also be within a range between and including any two of the values recited above. For example, the molecular weight range may be from about 1,000 daltons to about 25,000 daltons.

In some embodiments, the prepolymer is selected based on its absolute viscosity. For example, the viscosity of the prepolymer can be one of the following values or about/approximately (e.g., ± 0.5Pa · s) one of the following values: 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 44, 45, 47, 48, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 99 or 100 Pa. The viscosity can range between and include any two of the values recited above. For example, in one embodiment, the viscosity may range from about 0.5Pa · s to about 50Pa · s.

In some embodiments, the prepolymer is formed by the reaction of a polyol and a polyacid. In one embodiment, the polyol may be one or a combination of compounds including two or more hydroxyl groups, including diols, alkanediols, triols, glycerol, trimethylolpropane, triethanolamine, tetrols, erythritol, pentaerythritol, sorbitol, unsaturated diols, tetradecyl-2, 12-diene-1, 1, 14-diol, macromer diol, polyethylene oxide, or N-methyldiethanolamine. In one embodiment, the polyacid may be a diacid or higher order acid and include, for example, glutaric acid, adipic acid, pimelic acid, suberic acid, and azelaic acid. Exemplary long chain acids may include diacids having 5 or more, 10 or more, 15 or more, 20 or more, or 25 or more carbon atoms.

In some embodiments, the prepolymer is a poly (glycerol sebacate) (PGS) prepolymer prepared by polycondensation of equimolar amounts of glycerol and sebacic acid.

In some embodiments, the adhesive further comprises an initiator in combination with the prepolymer. In some embodiments, the initiator is a photoinitiator, wherein the photoinitiator is selected from the group consisting of 2-dimethoxy-2-phenyl-acetophenone, 2-hydroxy-1- [4- (hydroxyethoxy) phenyl]-2-methyl-1-propanone (

2959) 1-hydroxycyclohexyl-1-phenyl ketone (b)

184) 2-hydroxy-2-methyl-1-phenyl-1-propanone (a)

1173) 2-benzyl-2- (dimethylamino) -1- [ 4-morpholinyl) phenyl]1-butanone (Irgacure 369), methyl benzoylformate (I), (II), (III), (IV

MBF), oxy-phenyl-acetic acid-2- [ 2-oxy-2-phenyl-acetoxy-ethoxy]-ethyl ester(s) (iii)

754) 2-methyl-1- [4- (methylthio) phenyl group]-2- (4-morpholinyl) -1-propanone (C)

907) Diphenyl (2,4, 6-trimethylbenzoyl) -phosphine oxide(s) (II)

TPO), phosphine oxide, phenyl bis (2,4, 6-trimethylbenzoyl) ((R)

819) And combinations thereof. In one embodiment, the preferred photoinitiator is

2959。

In some embodiments, the prepolymer is stable and does not spontaneously crosslink within a body fluid (e.g., blood) when exposed to the fluid, without exposure to one or more external stimuli such as electromagnetic radiation, heat, chemical initiators, and the like. In one embodiment, the prepolymer is crosslinked by photopolymerization via exposure to electromagnetic radiation, such as visible or UV light. In these embodiments, the exposure time may be varied in order to achieve the desired amount of crosslinking. In some embodiments, the irradiation time may be 1 second or about 1 second (e.g., ± 0.5 seconds), 5 seconds or about 5 seconds (e.g., ± 1 second), 10 seconds or about 10 seconds (e.g., ± 2 seconds), 15 seconds or about 15 seconds (e.g., ± 2 seconds), 20 seconds or about 20 seconds (e.g., ± 3 seconds), 30 seconds or about 30 seconds (e.g., ± 3 seconds), 45 seconds or about 45 seconds (e.g., ± 4 seconds), 1 minute or about 1 minute (e.g., ± 5 seconds), 90 seconds or about 90 seconds (e.g., ± 5 seconds) or two or about two minutes (e.g., ± 10 seconds) or more. The irradiation time may be within a range between and including any two of those listed above.

In some embodiments, the intensity of light is varied as needed to achieve sufficient crosslinking. In one embodiment, the intensity may be less than about 0.45W/cm²。

In some embodiments, the crosslink density of the cured polymer may be adjusted by varying the degree of activation of the prepolymer, e.g., the degree of acrylation, or by varying the curing conditions such as curing time and energy intensity applied to cure the prepolymer. It is believed that higher bond strengths are achieved by higher levels of crosslinking.

In some embodiments, the crosslinked polymer may have a crosslink density of one or about/approximately (e.g., an amount of the listed values ± 10%) of one of the following values: 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. The crosslink density of the resulting crosslinked polymer can range between and include any two of the values recited above.

In some embodiments, the resulting crosslinked polymer will adhere to wet tissue. For example, in one embodiment, the cross-linked polymer will have sufficient adhesive strength to secure/join the native leaflets together (e.g., secure/join the anterior and posterior

mitral leaflets

114a, 114b together, e.g., near the a2-P2 segment thereof) without the need for additional securing mechanisms, such as sutures or staples. In some embodiments, the adhesive strength of the crosslinked polymer is one of the following values or about/approximately (e.g., the amount of the listed values ± 10%) one of the following values: 0.001N/cm²、0.002N/cm²、0.003N/cm²、0.004N/cm²、0.005N/cm²、0.006N/cm²、0.007N/cm²、0.008N/cm²、0.009N/cm²、0.01N/cm²、0.02N/cm²、0.03N/cm²、0.04N/cm²、0.05N/cm²、0.06N/cm²、0.07N/cm²、0.08N/cm²、0.09N/cm²、0.1N/cm²、0.2N/cm²、0.3N/cm²、0.4N/cm²、0.5N/cm²、0.6N/cm²、0.7N/cm²、0.8N/cm²、0.9N/cm²、1.0N/cm²、1.1N/cm²、1.2N/cm²、1.3N/cm²、1.4N/cm²、1.5N/cm²、1.6N/cm²、1.7N/cm²、1.8N/cm²、1.9N/cm²、2.0N/cm²、2.1N/cm²、2.2N/cm²、2.3N/cm²、2.4N/cm²、2.5N/cm²、2.6N/cm²、2.7N/cm²、2.8N/cm²、2.9N/cm²、3.0N/cm²、3.5N/cm²、4.0N/cm²、4.5N/cm²、5.0N/cm²、5.5N/cm²、6.0N/cm²、6.5N/cm²、7.0N/cm²、7.5N/cm²、8.0N/cm²、8.5N/cm²、9.0N/cm²、9.5N/cm²Or 10.0N/cm². The adhesive strength of the crosslinked polymer can range between and include any two of the values recited above.

With continued reference to fig. 1A-1D, the delivery device 100 may additionally include one or more energy elements 120 (although described, for example, with respect to energy elements, other types of curing elements may also be used) configured to cure adhesive dispensed from the applicator 106 and applied to the native heart valve (e.g., between the anterior and posterior

mitral leaflets

114a, 114 b). In some embodiments, one or more curing or energy elements 120 may be positioned on one or more portions of the upper surface (first end) 116 of the capsule 104. In an exemplary embodiment, such as shown in the top view of fig. 1D, a plurality of energy elements 120 may be located on the upper surface 116 of the capsule 104 and spaced substantially around the base of the applicator 106 or at equally spaced locations around the applicator 106. In one embodiment, six energy elements are placed in a circular arrangement around the applicator 106, with each pair of adjacent energy elements being equidistant from each other. The configuration and/or number of curing elements or energy elements 120 is not limited by the embodiment shown in fig. 1D, and different numbers may be used for similar or different arrangements. For clarity, the native leaflets or anterior and posterior

mitral leaflets

114a, 114b, and the adhesive 118 applied thereto from the applicator 106, are not shown in fig. 1D.

In some embodiments, the energy elements 120 will provide thermal energy (e.g., heat), while in other embodiments, the energy elements 120 will provide electromagnetic radiation (e.g., UV or visible light), while in certain other embodiments, the energy elements 120 will provide a combination of both thermal energy and electromagnetic radiation. As one example, all, some, or one of the one or more energy elements 120 can be configured or adjusted to provide electromagnetic radiation, such as visible light or Ultraviolet (UV) light. Similarly, all, some, or one of the one or more energy elements 120 may be configured or adjusted to provide visible light (e.g., blue light). In one embodiment, all, some, or one of the one or more energy elements 120 provide UV light.

In embodiments in which at least one of the energy elements 120 provides electromagnetic radiation (e.g., visible or UV light), the angle θ at which electromagnetic radiation is emitted from the energy element relative to a central axis (e.g., the z-axis as shown in fig. 1A-1D) may be one of the following or about/approximately (e.g., the amount of the listed values ± 10%) one of the following: 0 °, ± 1 °, ± 2 °, ± 3 °, ± 4 °, ± 5 °, ± 6 °, ± 7 °, ± 8 °, ± 9 °, ± 10 °, ± 11 °, ± 12 °, ± 13 °, ± 14 °, ± 15 °, ± 16 °, ± 17 °, ± 18 °, ± 19 °, ± 20 °, ± 22 °, ± 24 °, ± 26 °, ± 28 °, ± 30 °, ± 32 °, ± 34 °, ± 36 °, ± 38 °, ± 40 °, ± 42 °, ± 44 °, ± 46 °, ± 48 °, ± 50 °, ± 52 °, ± 54 °, ± 56 °, ± 58 °, ± 60 °, ± 62 °, ± 64 °, ± 66 °, ± 68 °, ± 70 °, ± 72 °, ± 74 °, ± 76 °, ± 78 °, ± 80 °, ± 82 °, ± 86 °, ± 88 °, ± 86 °, ±. Optionally, the angle θ can range between and include any two of the values recited above.

In some embodiments in which the at least one energy element 120 provides electromagnetic radiation (e.g., visible or UV light), one or more portions of the upper surface 116 of the capsule 104 may include one or more of the following: an energy reflective surface, an energy reflective coating, a light reflective surface and/or a light reflective coating. In one embodiment, the entirety of the upper surface 116 of the capsule 104 may include an energy reflective surface, an energy reflective coating, a light reflective surface, and/or a light reflective coating.

In some embodiments, the applicator 106 may comprise a porous material, and the porous material of the applicator 106 may be a light transmissive material configured to allow electromagnetic radiation (e.g., visible or UV light) emitted from the one or more energy elements 120 to be incident on the adhesive remaining within the applicator 106. For example, the transmittance of light through the porous material of the applicator 106 may be at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100%. Additionally, the transmittance of the porous material through the applicator 106 can range between and include any of the two values described above.

In some embodiments, the applicator 106 may be separate from the capsule 104. In one embodiment, once the capture parts or leaves 102a, 102b are moved to the closed configuration and the adhesive 118 is applied in the space between the capture leaflets (e.g., 114a, 114b) via the applicator 106, one or more curing or energy elements 120 can be activated ("energized") to cure the applied adhesive 118. After curing, the delivery device 100 may be withdrawn (e.g., from the heart and further from the patient) and the applicator 106 physically separated from the capsule 104. In some embodiments, the capture features or

leaflets

102a, 102b can move from the closed configuration to the open configuration (or an intermediate configuration therebetween) when the delivery device 100 is withdrawn from the immediate vicinity of the native or

mitral leaflets

114a, 114 b. The catch pieces or leaves 102a, 102b may then be moved back to the closed configuration to have a smaller profile during withdrawal or further withdrawal of the delivery device 100 from the patient.

Fig. 2 provides an example in which the delivery device 100 is in the process of being withdrawn in an open configuration with the capture features or

blades

102a, 102b, and in which the applicator 106 is separated from the capsule 104. In some embodiments, after withdrawal of the delivery device 100, the separate applicator 106 will remain between the native leaflets (e.g., anterior and posterior

mitral leaflets

114a, 114 b). In these embodiments, the leaflets are sealed together at least via a cured adhesive 118, the cured adhesive 118 being located between the leaflets and which may be present on one or more outer and/or inner portions of the applicator 106 (see fig. 3).

In embodiments in which the applicator 106 is held between the native or

mitral leaflets

114a, 114b, as shown in fig. 3, the applicator 106 will preferably be composed of a biocompatible material. In some embodiments, the material of the detachable applicator 106 is both biocompatible and biodegradable (e.g., bioabsorbable). Over time, degradation (or absorption) of the applicator 106 will not affect the integrity of the cured adhesive 118 applied between the native leaflet or anterior mitral and posterior

mitral leaflets

114a, 114b (e.g., will not weaken or otherwise adversely affect). For example, a cured adhesive 118 may be present between the outer portion of applicator 106 and native or

mitral valve leaflets

114a, 114b, as well as within applicator 106. Thus, the cured adhesive 118 on the outer portion of the applicator 106 may contact and adhere to the native or

mitral valve leaflets

114a, 114 b. Given that the applicator 106 is preferably composed of a porous material, the cured adhesive 118 on the outer portion of the applicator 106 may also contact and adhere to the cured adhesive 118 present within the applicator 106. Thus, degradation of the porous material of the applicator 106 will not affect the adhesion between the cured adhesive 118, and the cured adhesive 118 is used to join the native or

mitral leaflets

114a, 114 b.

Additionally, in some embodiments with a detachable applicator 106, the applicator will include a material that promotes tissue growth and natural fusion of the leaflets (e.g., 114a, 114 b). In these embodiments, the material will promote tissue growth into the scaffold or will include regenerated tissue that the body incorporates into itself. Examples of suitable regenerated tissue include, but are not limited to, decellularized tissue, polylactan, collagen, and polyglycolic acid. In embodiments using polyglycolic acid scaffolds, the polyglycolic acid scaffolds are bioabsorbable, and the extracellular matrix proteins will allow for the seeding of the host's tissue for incorporation into the body of the patient of the regenerated tissue. Examples of suitable extracellular matrix proteins include, but are not limited to, hydroxyproline, vitronectin, fibronectin, and collagen type I, collagen type III, collagen type IV, collagen VI, collagen XI, collagen XII, fibrillin I, tenascin, decorin, byglycan, pluripotent proteoglycan, agaosporin, and combinations thereof. In some embodiments, the polyglycolic acid scaffold will include extracellular matrix proteins within the scaffold, while in other embodiments, the extracellular matrix proteins will coat the polyglycolic acid scaffold with extracellular matrix proteins. In yet a further embodiment, the extracellular matrix protein will be both within and coating a polyglycolic acid scaffold.

In various embodiments, applicator 106 and/or adhesive 118 will include a tissue growth enhancing agent or growth factor that will stimulate or promote tissue ingrowth into applicator 106 or tissue growth for fusion of the valve leaflets (e.g., 114a, 114 b). examples of suitable growth enhancing agents include, but are not limited to, transforming growth factor α (TGF- α), transforming growth factor β (TGF- β), basic fibroblast growth factor (bFGF), Vascular Epithelial Growth Factor (VEGF), and combinations thereof.

In some embodiments, the applicator 106 is configured to retract within the lumen of the capsule 104. In one such embodiment, once the capture parts or

leaflets

102a, 102b are moved to the closed configuration and the adhesive 118 is applied in the space between the captured leaflets (e.g., 114a, 114b) via the applicator 106, the applicator 106 can be partially or fully retracted within the capsule 104.

Fig. 4 provides an example in which the applicator 106 is in the process of being retracted within the inner lumen of the capsule 104 after the adhesive 118 is dispensed between the captured native or

mitral leaflets

114a, 114 b. After the applicator 106 has been partially or fully retracted within the capsule 104, one or more energy elements 120 may be activated ("energized") to cure the applied adhesive 118. After curing, the delivery device 100 may be withdrawn (e.g., from the heart) to seal the native leaflets (e.g., anterior and posterior

mitral leaflets

114a, 114b) together via the cured adhesive 118 located between the leaflets (see fig. 5). In some embodiments, the capture features or

leaflets

102a, 102b can move from the closed configuration to the open configuration (or an intermediate configuration therebetween) when the delivery device 100 is released and/or withdrawn from the immediate area of the native or

mitral leaflets

114a, 114 b. The catch pieces or leaves 102a, 102b may then optionally be moved back to the closed configuration for further withdrawal of the delivery device 100 from the patient in a smaller profile.

With continued reference to fig. 1A-1D, the delivery device 100 includes an arm 108 coupled to a second end 130 of the capsule 104. In some embodiments, the arms 108 can include a suitable length that enables the capture parts or

leaflets

102a, 102b to be advanced through the patient's heart (e.g., through the left ventricular chamber) and positioned between the native leaflets (e.g., anterior and posterior

mitral leaflets

114a, 114 b). The capture features or

leaflets

102a, 102b are preferably positioned so as to be able to contact and capture the native leaflet at its desired location (e.g., captured anterior and posterior

mitral leaflets

114a, 114b near the middle segment (e.g., segment a 2-P2)). Further, in various embodiments, the arm 108 is composed of a material that is sufficiently rigid to support the capsule 104, applicator tip 106, and capture features or

blades

102a, 102b, yet sufficiently flexible or pliable to allow the arm 108 to be advanced through certain portions of the heart.

In various embodiments, the arm 108 includes a handle 122 located opposite the end connected to the capsule 104, as shown in the exemplary embodiment in fig. 6. The handle 122 includes a suitable shape and size to enable a physician or other medical professional to grasp the handle 122 by hand and guide the arm 108 through a desired region of the patient's heart. The handle 122 may also include one or more power buttons (not shown in fig. 6) that may be actuated in an on/off position to control dispensing of the adhesive 118 via the applicator 106, to control the function of the energy element 120 (e.g., turning the power on/off), to control actuation of the capture features or

blades

102a, 102b, and/or to control the function of any other component operably connected to the delivery device 100.

In some embodiments, the capsule 104, the arm 108, and the optional handle 122 have substantially the same width as one another, while in some embodiments the width of the arm 108 is less than the width of the capsule 104 and/or the handle 122.

In some embodiments, the capsule 104, the arm 108, and/or the optional handle 122 represent portions of a single continuous structure (part). In some embodiments, the arm 108 is a separate component from the capsule 104 and/or the optional handle 122.

In some embodiments, each of the capsule 104, the arm 108, and/or the optional handle 122 can include one or more lumens/cavities. In some embodiments, one or more lumens may extend through the capsule 104, the arm 108, and/or the optional handle 122. These lumens may be coaxial, arranged side-by-side, or a combination thereof.

Fig. 7 illustrates an exemplary configuration of one or more lumens/cavities present within and extending through the capsule 104, the arm 108, and the optional handle 122. For clarity, the outer peripheries of the capsule 104, the arm 108, and the optional handle 122 are indicated in dashed lines. It should be noted that fig. 7 is for exemplary purposes only and describes various features that may be incorporated into embodiments of the present disclosure.

As shown in particular in fig. 7, an adhesive delivery assembly 702 is provided in one such lumen/cavity. The adhesive delivery assembly 702 may include a sleeve 704 containing an adhesive. In some embodiments, the sleeve 704 comprises two

chambers

704a, 704b, wherein one chamber comprises a prepolymer as discussed herein and the other chamber comprises an initiator as discussed herein. In some embodiments, sleeve 704 is also in fluid communication with applicator 106, and thus is capable of being supplied/fed with adhesive. For example, the adhesive delivery assembly 702 may include one or

more chambers

706a, 706b configured to transfer the pre-polymer and the initiating agent, respectively, from the sleeve 704 to the applicator 106. While the sleeve 704 may be housed in the optional handle 122 of the delivery device 100, as shown in fig. 7, in some embodiments, the sleeve 704 may be housed in a portion of the arm 108 or the capsule 104.

The adhesive contained within the sleeve 704 described above may be transferred to the applicator 106 via a variety of means. In some embodiments, the sleeve 704 is connected to a piston mechanism (e.g., a plunger) configured to reduce the volume (and thereby increase the pressure) within the sleeve 704, thereby forcing adhesive from the sleeve 704 toward and into the applicator 106. The piston mechanism may be activated electronically (e.g., via a power button present on optional handle 122 or arm 108) or mechanically.

In some embodiments, the sleeve 704 is connected to a source of compressed gas or air that, when activated, provides compressed gas or air to the sleeve 704 to force the adhesive toward and into the applicator 106. In various embodiments, a power button (e.g., on optional handle 122 or arm 108) is actuated in an on/off position to control the generation of compressed air within the cartridge. In such embodiments, a pressure regulator (e.g., connected to the sleeve 704 and/or a source of compressed air) is used to regulate the amount of pressure applied to the sleeve 704 to force the adhesive out of the sleeve and toward and into the applicator 106. It is noted, however, that the adhesive may be supplied to the applicator 106 via other means, as will be recognized by the skilled artisan upon review of the present disclosure.

As also shown in fig. 7, the delivery device 100 includes a connection means 708 (e.g., electrical conductor/wire, wireless connection, RFID, etc.) that operatively connects the energy element 120 to the energy/power source. The connection tool 708 may be housed in a lumen/cavity extending from the capsule 104, the arm 108, and/or the optional handle 122. In some embodiments, the energy source 120 is connected via a connection means to a power button present on the optional handle 122 or arm 108.

In embodiments where at least one energy element 120 is configured to provide electromagnetic radiation, the energy element may be an optical fiber. In some embodiments, the optical fiber extends from the upper surface 116 of the capsule 104 through the arm 108 (and optional handle 122, if present).

Additionally, the delivery device 100 may include an actuation system, a portion of which may reside in the sealed compartment 104, the arm 108, and/or the lumen/cavity of the optional handle 122. In some embodiments, the actuation system is connected and configured to actuate the capture features or

blades

102a, 102 b. The actuation system may include any suitable actuation element(s), such as gears, shafts, pulleys, screws, nuts, spindles, shafts, wheels, and the like. The actuation system may also include an electric actuator (e.g., a motor such as a DC brushed motor, a brushless motor, an AC motor, a servo motor, a stepper motor, etc.), a hydraulic transmission, a pneumatic actuator, and/or a mechanical actuator, among others. In some embodiments, a single actuation system (and motor) is configured to actuate each capture part (e.g., two

blades

102a, 102 b). In some embodiments, each capturing part or

blade

102a, 102b is independently actuated via a separate actuation system (and, e.g., a respective motor, pulley, etc.). For example, in one embodiment, each catch part or

vane

102a, 102b is actuated by one or more servo motors between an open configuration and a closed configuration, allowing precise linear and/or rotational movement. An example of an actuation system for transcatheter delivery is illustrated and described in U.S. patent publication No. US 2017/0231756a1, wherein the portions related to actuation are incorporated herein by reference

Further, a connection means (e.g., electrical conductors/wires) may operatively connect the capturing parts or

blades

102a, 102b and the actuation system to an energy/power source. The attachment tool may be housed in a lumen extending from the capsule 104 and through the arm 108 (and optional handle 122, if present). In some embodiments, the catch pieces or

blades

102a, 102b and the actuation system may be connected via a connection means to a power button present on the optional handle 122 or arm 108.

It is noted that the delivery device 100 and its components are not limited to the configuration shown in fig. 1A-1D-7. For example, fig. 8-15 illustrate a variation of the delivery device 100, such as shown in fig. 1A-1D-7, wherein the same or similar components and features are given the same reference numerals. It is noted that the devices/components/features described in fig. 8-15 may be implemented in combination with or as an alternative to the devices/components/features described herein, such as those described with reference to other embodiments and the accompanying drawings. The delivery devices of fig. 8-15 may additionally be used in any method of making and/or using such devices described herein.

As shown in the embodiment in fig. 8, the delivery device 800 includes a delivery sheath 802 (delivery catheter). In embodiments that include a delivery sheath 802, the delivery sheath 802 is sized to enable retraction of the catch pieces or

blades

102a, 102b (in the open or closed configuration), the capsule 104, and the applicator 106 therein. In some embodiments, the delivery sheath 802 extends along at least a portion of the arm 108 (e.g., longitudinally), while in some embodiments, the delivery sheath 802 will extend the entire length of the arm 108.

Incorporation of the delivery sheath 802 may be advantageous for transporting the delivery device 800 through the heart. For example, during insertion of the delivery device 800 into a patient, the capture features or

blades

102a, 102b (in an open configuration or a closed configuration), the capsule 104, and the applicator 106 may be present in the lumen/cavity of the delivery sheath 802. Once the delivery device 800 is introduced into the heart (e.g., left ventricle) and positioned adjacent to the native leaflets (e.g.,

mitral valve leaflets

114a, 114b), the capture features or

leaflets

102a, 102b (in the open or closed configuration), the capsule 104, and the applicator 106 can be extended from the delivery sheath 802. As previously discussed, the capture features or leaves 102a, 102b can then be actuated to capture the leaflets (e.g., 114a, 114b) and pull the leaflets together to allow the adhesive 118 to be applied therebetween via the applicator 106. After applying the adhesive and/or curing the adhesive via the energy element 120, the capture features or

blades

102a, 102b, the capsule 104, and the applicator 106 (if not separated) may again be retracted within the delivery sheath 802 to allow the delivery device 800 to be easily withdrawn from the patient.

As shown in the embodiment in fig. 9, in some embodiments, the delivery device 900 includes a capture part or

blade

102a, 102b having an

attachment portion

110a, 110b connected to the upper surface (first end) 116 of the capsule 104 with the applicator 106 positioned therebetween. As illustrated in fig. 9, some embodiments size the capsule 104 to enable the capture parts or

blades

102a, 102b (in the open or closed configuration) and the applicator 106 (if not separated) to be retracted therein. In some embodiments, the delivery device 900 includes a delivery sheath having a lumen sized to allow the capture features or

blades

102a, 102b (in an open configuration or a closed configuration), the capsule 104, and the applicator 106 to be retracted therein, as discussed with reference to fig. 8.

Fig. 10-14 illustrate embodiments in which the capture features (e.g., blades) of the delivery system have different overall shapes and/or widths as otherwise described herein. For example, as shown in the side view in fig. 10, the delivery system 1000 may include capture features or blades 1002a, 1002b, each extending in a substantially linear manner from an attachment portion 1004a, 1004b to an

end

1006a, 1006b thereof. The capture features or blades 1002a, 1002b of the delivery device 1000 do not include the different angled sections of the capture features or

blades

102a, 102b of the delivery device 100 (see, e.g., fig. 1A-1D). In various embodiments, the linear capture features or blades 1002a, 1002b of the delivery device 1000 are attached to the sides of the capsule 104, for example, as shown in fig. 10. In some embodiments, the linear capture features or blades 1002a, 1002b of the delivery device 1000 are attached to the upper surface 116 of the capsule 104, as described with reference to fig. 9. In some embodiments, the delivery device 1000 is also used in conjunction with a delivery sheath 802, as described with reference to fig. 8.

As shown in the exemplary embodiment in fig. 11, some embodiments of a delivery system (e.g., delivery system 100) include capture features or blades 1102a, 1102b having a non-uniform width extending along a longitudinal direction. For clarity, there is no delivery device attached in fig. 11, and the inner surfaces of the capture features or leaflets 1102a, 1102b (i.e., the surfaces facing and contacting the native or mitral leaflets) are shown. As illustrated in fig. 11, the

end

1104a, 1104b of each capture feature or blade 1102a, 1102b may have a substantially circular shape. In some embodiments, the

end portion

1104a, 1104b of each capture part or leaflet 1102a, 1102b has a means to assist in contacting and/or gripping the native valve leaflet (e.g., 114a, 114 b). Such tools include, but are not limited to, textured surfaces and/or coatings. The textured surface may include ridges (ridges), cutaways (catches), or any pattern that may assist and/or increase the effectiveness of gripping the native valve leaflets. The coating may include a temporary and/or weak adhesive that may temporarily hold the native valve leaflets with minimal or no damage to the native tissue. Additionally, the

rounded end

1104a, 1104b of each capture part or leaf 1102a, 1102b in some embodiments is comprised of cloth or woven mesh. It is noted that the

ends

1104a, 1104b of each capture feature or leaflet 1102a, 1102b are not limited to a circular shape and may include any shape configured for convenient capture of a native or mitral valve leaflet, as will be recognized by those skilled in the art upon review of the present disclosure.

Turning now to fig. 12, an illustration of one embodiment of a delivery device is depicted. In the embodiment in fig. 12, the

native valve leaflets

114a, 114b are captured using

inflatable balloons

1230a, 1230b rather than using mechanical opening and closing of the capture features or

leaflets

1202a, 1202 b. In embodiments utilizing an

inflatable balloon

1230a, 1230b, an inflation fluid will be pumped into the

inflatable balloon

1230a, 1230b to reduce the distance between the

ends

1212a, 1212 b. As such,

inflatable balloons

1230a, 1230b will press

leaflets

114a, 114b to contact applicator 106, which will allow adhesive 118 to contact

leaflets

114a, 114 b. The use of

inflatable balloons

1230a, 1230b may be beneficial where mechanical movement, such as through joints (see fig. 1C and associated text), may present problems in the valve repair field, such as contamination, wear, and/or other limitations.

Referring now to fig. 13A-13B, a delivery device 1300 configured to apply adhesive between the posterior mitral leaflet and the anterior mitral leaflet is shown according to one embodiment. The delivery device 1300 may include similar features to those previously described. However, while the delivery device depicted in the foregoing figures is configured so as to facilitate left ventricular delivery/delivery, the delivery device 1300 in fig. 13A-13B is configured for transvascular and transseptal left atrial delivery. It is noted that the delivery device 1300 and its components/parts described in fig. 13A-13B may be implemented in combination with or as an alternative to the devices/components/parts described herein, such as those described with reference to the other embodiments and figures. It is further noted that like parts and features are assigned like reference numerals. The delivery device 1300 may also be used in various applications and/or arrangements, which may or may not be mentioned in the illustrative embodiments described herein. For example, in some embodiments, the delivery device 1300 may include more or fewer parts/components than those shown in fig. 13A-13B. Further, the delivery device 1300 is not limited to the size, shape, number, etc. of the components specifically shown in fig. 13A-13B.

As shown in the side view in fig. 13A, the delivery device 1300 includes capture features 1302 for capturing native leaflets, e.g., the anterior and posterior

mitral leaflets

114a, 114 b. In some embodiments, each capture feature 1302 includes a pair of

leaflets

1302a, 1302b, each leaflet including at least two clips configured to contact, capture (e.g., "hook") and move a native or mitral leaflet. For example, FIG. 13B provides a clip 1302a formed from a leaf 1302a₁And 1302a₂(note that the leaflet 1302b and its associated clip are not shown for clarity) an interior view of the captured ("hooked") mitral valve anterior leaflet 114 a. In various embodiments, the clip of each leaflet 1302a, 1302b is specifically sized/shaped to capture a mitral valve leaflet. For example, as shown in the embodiment of fig. 13A-13B, each clip may be substantially U-shaped.

In some embodiments, the

blades

1302a, 1302b may be movable from an open configuration to a closed configuration. In the open configuration, ends 1304a, 1304b of each

blade

1302a, 1302 are separated by a first distance. In some embodiments, the first distance corresponds to a maximum distance that ends 1304a, 1304b of

blades

1302a, 1302b may be separated from one another. In some embodiments, the first distance is sufficient to enable the

leaflets

1302a, 1302b to contact and capture the anterior and posterior

mitral leaflets

114a, 114 b.

In the closed configuration, the

ends

1304a, 1304b of each

blade

1302a, 1302b are separated by a second distance that is less than the first distance described above. In some embodiments, the second distance is the minimum distance that the

ends

1304a, 1304b of the

blades

1302a, 1302b can be separated from each other. In some embodiments, ends 1304a, 1304b of

blades

1302a, 1302b are separated by the second distance resulting in the ends being in contact or in close proximity to each other.

In some embodiments, the

leaflets

1302a, 1302 are in an open configuration to contact and capture the anterior and posterior

mitral leaflets

114a, 114b when positioned in the left atrial chamber of the heart, and then move to a closed configuration to draw/move the

leaflets

114a, 114b together so as to apply adhesive therebetween. In situations where the anterior and

posterior leaflets

114a, 114b need to be readjusted relative to the delivery device 1300, the

leaflets

1302a, 1302b may be opened and closed until an optimal position and/or depth of engagement is achieved.

Further, in various embodiments, the

blades

1302a, 1302b are configured to move and/or rotate in various directions independently of other capturing parts or

blades

1302a, 1302b, such as described with respect to fig. 1A-1D. For example, in some embodiments, each blade 1302a, 1302B may be independently configured to move in at least a direction parallel to the x-axis and/or y-axis shown in fig. 13A-13B. In some embodiments, each

blade

1302a, 1302b is also independently rotatable about the y-axis by a predetermined amount.

In some embodiments, the blade 1302a moves independently of the blade 1302 b. However, in some embodiments, the two

blades

1302a, 1302b move in unison such that movement of one blade causes, and/or is associated with a mirrored movement of the other blade.

In some embodiments, each clip of the

blades

1302a, 1302b moves independently of the other. For example, in one embodiment, the delivery device 1300 does not include leaflets, but rather other capture features, such as four separate clips that can be independently manipulated to capture a portion of a mitral valve leaflet.

In various embodiments, the movement and/or rotation of the catch parts or

blades

1302a, 1302b and/or individual clips is accomplished via various mechanical means, such as disclosed herein with respect to fig. 1A-1D-7. For example, in some embodiments, each capture part or

blade

1302a, 1302b or each individual clip is connected to a portion of the delivery system via a joint that allows movement and/or rotation of the components.

As also shown in fig. 13A-13B, the delivery device 1300 includes an applicator 106 extending from the upper surface (first end) 116 of the capsule 104. As disclosed herein with respect to various embodiments, such an applicator 106 is specifically configured to be positioned/inserted between native leaflets (e.g., between the anterior and posterior

mitral leaflets

114a, 114b) that are captured between the capture features or

leaflets

1302a, 1302 b. Further, the applicator 106 may be configured to distribute/apply adhesive between the captured leaflets or anterior and posterior

mitral leaflets

114a, 114 b. To this end, in various embodiments, the capture parts or

leaflets

1302a, 1302b can be moved to a closed configuration such that the sidewalls of the applicator 106 contact and/or are in close proximity to at least a portion of the captured leaflet or

mitral leaflet

114a, 114b, thereby enabling adhesive to be applied directly to the portion of the

leaflet

114a, 114b via the applicator 106. In some embodiments, adhesive is applied to the middle section of the

mitral valve leaflets

114a, 114b (e.g., the a2-P2 section) via applicator 106.

In some embodiments, the applicator 106 is detachable from the capsule 104. In some embodiments, the applicator 106 is configured to partially or fully retract within the capsule 104.

Further, in various embodiments, the delivery device 1300 additionally includes one or more curing or energy elements (such as in fig. 1D) configured to cure the adhesive dispensed from the applicator 106 and applied between the native or anterior mitral and posterior

mitral leaflets

114a, 114 b. In some embodiments, one or more energy elements may be positioned on one or more portions of the upper surface (first end) 116 of the capsule 104. In an exemplary embodiment, the plurality of energy elements are located on the upper surface 116 of the capsule 104 and are spaced substantially around the base of the applicator 106 and/or at equally spaced locations around the base of the applicator 106.

In various embodiments, the delivery device 1300 includes an arm (such as illustrated in fig. 1A-1C) connected to the second end of the capsule 104. In some embodiments, the capture pieces or

blades

1302a, 1302b are attached to at least a portion of the arm, or to at least a portion of the capsule 104.

Further details and embodiments of the configurations, materials and functions of any of the above-described related applicators 106, adhesives dispensed therefrom, the capsule 104, the energy element, the arm, and the lumen/cavity described with respect to the

delivery devices

100, 800, 900, 1000, and 1400 in fig. 1A-1D through 10 and 14 may be incorporated into the delivery device 1300 in fig. 13A-13B.

As shown in fig. 13A-13B, various embodiments of the delivery device 1300 include a microcatheter 1306 to enclose at least a portion of each capture feature or blade 1302a, 1302B.

As additionally shown in fig. 13B, some embodiments of the delivery device 1300 further include a delivery sheath/catheter 1308. In such embodiments, the delivery sheath 1308 is sized to enable the capture elements or

blades

1302a, 1302b (in the open or closed configuration), the capsule 104, and the applicator 106 to be retracted therein. The delivery sheath 1308 can extend along at least a portion of or the entire length of the arms of the delivery device 1300 (e.g., longitudinally).

Incorporation of the delivery sheath 1308 may be advantageous for the delivery device 1300 to transmit through the heart. For example, the capture features or

blades

1302a, 1302b, the capsule 104, and the applicator 106 may be present in the lumen/cavity of the delivery sheath 1308 during insertion of the delivery device 1300 into a patient. Once the delivery device 1300 is introduced into the left atrial chamber and positioned adjacent the

mitral valve leaflets

114a, 114b, the clips of the

leaflets

1302a, 1302b can extend from the delivery sheath 1308 into the mitral valve toward the left ventricle and actuate to capture the mitral valve leaflets via the four clips and form a "pocket. The capsule 104 and applicator 106 can also extend from the delivery sheath 1308 to allow application of adhesive via the applicator 106 to capture mitral valve leaflets, and subsequently cure the applied adhesive via an energy element located on the capsule 104. Once the adhesive is cured, the

blades

1302a, 1302b, capsule 104, and applicator 106 (if not separated) may again be retracted within the delivery sheath 1308 to allow the delivery device 1300 to be easily withdrawn from the patient. Similar steps and features may be used to apply adhesive to other native valves.

Turning now to fig. 14, an embodiment of a delivery device 1400 including three capture features or

vanes

102a, 102b, 102c is illustrated in a top view. Embodiments having a 3-leaflet configuration may be used with a native valve that includes 3 leaflets, such as an aortic valve, a tricuspid valve, and/or a pulmonary valve. In some embodiments, three capturing parts or

blades

102a, 102b, 102c are attached to the capsule 104, with the applicator 106 and the energy element 120 disposed on the capsule 104, in much the same manner as described in fig. 1D. In various embodiments, the delivery device 1400 is manipulated, changed, and/or operated similar to the configuration illustrated in fig. 1A-1D such that the capturing parts or

blades

102a, 102b, 102c can be operated simultaneously, with each capturing part or blade moving in a mirrored fashion to the other two capturing parts or blades. For example, manipulating the catch part or leaf 102a to the open position also manipulates the catch parts or leaves 102b and 102c to move to the open position. In some embodiments, each capturing part or blade moves independently of the other two capturing parts or blades. For example, manipulating the catch part or leaf 102a to an open position will have no effect on the position or state of the catch parts or leaves 102b and 102 c.

Further details and embodiments of the configurations, materials, and functions of any of the above-described related applicators 106, adhesives dispensed therefrom, the capsule 104, the energy element, the arm, and the lumen/cavity described with respect to the

delivery devices

100, 800, 900, 1000, and 1300 in fig. 1A-1D through 13 may be incorporated into the delivery device 1400 in fig. 14.

Turning now to fig. 15A-15B, some embodiments of the delivery device 100 include an expandable scaffold 1532. In the illustrated embodiment, the expandable scaffold 1532 is contained within a protective sheath 1534 as part of the arms 108 of the delivery device 100; however, some embodiments will have an expandable scaffold 1532 attached to a portion of the capsule 104. In the embodiment in fig. 15A, the protective sheath 1534 will be retracted from the delivery device 100, or the arms 108 will extend from the protective sheath 1534, which allows the expandable stent 1532 to expand. In some embodiments, the protective sheath 1534 may not be present and other mechanical means may be used to expand the expandable scaffold 1532 from the arm 108 and/or the capsule 104. In various embodiments, the protective sheath 1534 is the same as the delivery sheath 802 described with respect to fig. 8.

Turning now to fig. 15B, one embodiment including an expandable scaffold 1532 is illustrated. In this embodiment, an expandable scaffold 1532 is disposed around the inflatable balloon 1536. In the illustrated embodiment, the expandable scaffold 1532 and inflatable balloon 1536 are assembled around a portion of the arms 108 of the delivery device 100; however, some embodiments will have an expandable scaffold 1532 attached to a portion of the capsule 104. In embodiments that include an inflatable balloon 1536, the inflatable balloon 1536 will have a lumen in fluid communication with the lumen of the capsule 104 and/or the arm 108. Using this lumen, a suitable inflation fluid will be delivered to the inflatable balloon 1536, which allows the inflatable balloon 1536 to expand, thus causing expansion of the expandable stent 1532.

In embodiments including an expandable stent such as illustrated in fig. 15A-15B, the expandable stent 1532 is radially expanded when the delivery device 100 is positioned in the left ventricle or left atrium adjacent to native leaflets (e.g., mitral valve leaflets 114a, 114B) to provide stability to the delivery device 100 during capture of the valve leaflets, application and/or delivery of the adhesive 118 therebetween, and/or curing of the adhesive 118. In various embodiments, the expandable scaffold 1532 is retractable to allow the delivery device 100 to be easily withdrawn from the patient.

Referring now to fig. 16A-16C, an exemplary method of using a delivery device 1600 as described herein is shown. Although the method is generally illustrated with respect to a mitral valve, similar steps may be applied with respect to other native heart valves. As shown in fig. 16A, the delivery device 1600 is advanced through the aorta into the heart (e.g., toward the left atrium through the left ventricle of the heart) and positioned adjacent to native leaflets (e.g., the anterior mitral leaflet and the posterior mitral leaflet). The capture features (e.g.,

leaflets

1602a, 1602b) are then opened to contact and capture two or three native leaflets (e.g., mitral valve leaflets).

As illustrated in fig. 16B, the capture parts or leaves 1602a, 1602B are then moved to a closed configuration in order to draw the captured native leaflets (e.g., mitral valve leaflets) together to contact the applicator 1606. After the applicator 1606 is in contact with the leaflets, adhesive 1618 is dispensed between the captured leaflets via the applicator 1606. It is noted that if the leaflets need to be readjusted before the adhesive 1618 is applied thereto, the capture parts or

leaves

1602a, 1602b can be opened and closed until an optimal configuration and proper coaptation depth are achieved. After the adhesive 1618 is applied, the adhesive may be cured with a curing element, such as similar to those previously discussed.

Turning to fig. 16C, the delivery device 1600 can be removed from the patient after curing the adhesive 1618 via one or more curing or energy elements (e.g., UV light sources) associated with the delivery device 1600. At this stage, only the adhesive 1618 remains. However, in embodiments utilizing a detachable applicator, applicator 1606 may also remain between the native leaflets.

Turning now to fig. 17, an exemplary method of using a delivery device 1700 as described herein is shown. Although the method is generally illustrated with respect to a mitral valve, similar steps may be applied with respect to other native heart valves. As shown in fig. 17, delivery device 1700 is advanced and positioned adjacent to a native leaflet (e.g., anterior mitral leaflet and posterior mitral leaflet). To access the left atrium as illustrated in fig. 17, delivery device 1700 is navigated (navigator) to the right atrium and moved into the left atrium via a transseptal puncture. If the tricuspid valve is treated, this can be done from the right atrium without passing through the septum. While there are a number of ways to position the delivery device in the right atrium, various embodiments will navigate the delivery device 1700 transvascularly (e.g., via the inferior vena cava, superior vena cava, femoral vein, etc.). In one embodiment, delivery device 1700 is navigated via transfemoral delivery such that delivery device 1700 is navigated through the femoral vein, through the inferior vena cava, and into the right atrium. If the mitral valve is being treated, a transseptal puncture may be performed and the delivery device 1700 is passed from the right atrium to the left atrium through the transseptal puncture. In some embodiments, delivery device 1700 is then passed from the atrium to the ventricle (e.g., right atrium to right ventricle or left atrium to left ventricle). Once a desired chamber or other desired location of the heart is reached, the capture features (e.g.,

leaflets

1702a, 1702b) are opened to contact and capture two or three native leaflets (e.g., mitral valve leaflets, tricuspid valve leaflets, etc.).

Similar to that described with reference to fig. 16B, the capture pieces or leaflets 1702a, 1702B are then moved to the closed configuration in order to draw the captured native leaflets (e.g., mitral valve leaflets) together to contact the applicator 1706. After the applicator 1706 is in contact with the leaflets, adhesive is then dispensed between the captured leaflets via applicator 1606. It is noted that if the leaflets need to be readjusted prior to applying adhesive thereto, the capture features or

leaflets

1702a, 1702b can be opened and closed until an optimal configuration and proper coaptation depth are achieved. After the adhesive is applied, the adhesive may be cured with a curing element, such as similar to those previously discussed.

As described with respect to fig. 16C, the delivery device 1700 may be removed from the patient after curing the adhesive via one or more curing or energy elements (e.g., UV light sources) associated with the delivery device 1700. At this stage, only the adhesive and/or applicator remains.

After delivery of the adhesive via a delivery device as described herein, if there is residual valve regurgitation or mitral regurgitation after the adhesive is initially applied to the native or mitral valve leaflets and the composition is then cured, additional applications of the adhesive may be applied at other locations along the native valve leaflets (e.g., adjacent to or spaced apart from the previous fusion site). This application may be repeated multiple times to achieve a desired reduction in regurgitation (e.g., mitral regurgitation reduction).

Referring now to fig. 18A, a diagram of the definition of Carpentier for Mitral Valve (MV) anatomy is shown. In fig. 18A, the mitral anterior leaflet 1802 and the mitral posterior leaflet 1804 are illustrated in conjunction with the respective pits (dimples) of each mitral leaflet. In fig. 18A, a2 and P2 represent the intermediate pits of the anterior mitral valve leaflet 1802 and the posterior mitral valve leaflet 1804, respectively. Also marked are lateral pits (a1 and P1) and medial pits (A3 and P3). AC and PC denote the anterolateral and posteromedial commissures of the mitral valve MV.

Turning now to fig. 18B, a top view of the mitral valve anterior leaflet 1802 and mitral valve posterior leaflet 1804 fused together via cured adhesive 1818 is shown. In some embodiments, fusion is accomplished in the presence of the detachable applicator 1806. In some embodiments,

mitral valve leaflets

1802, 1804 are fused near the middle fovea of the leaflet, for example, at the a2-P2 segment of the leaflet as defined by Carpentier, as illustrated in fig. 18A. However, depending on the disease cause, the fusion of leaflets can be applied anywhere along the anterior commissure to restore the closing function of the valve.

In some embodiments, provided herein is a kit or delivery system comprising a delivery device as described herein and a curable adhesive for use therewith. In some embodiments, the kit or delivery system further comprises instructions on how to use the delivery device and/or curable adhesive.

***

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

Throughout the specification and claims, unless the context requires otherwise, the word "comprise" and variations such as "comprises" and "comprising" are to be interpreted in an open, inclusive sense, i.e., as "including but not limited to". In addition, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

Reference throughout this specification to a range of numerical values is intended to serve as a shorthand notation for referring individually to each separate value falling within the range including the value defining the range, and each separate value is incorporated into the specification as if it were individually recited herein.

References herein to "about" a value or parameter include (and describe) embodiments that are directed to that value or parameter itself. In some embodiments, the term "about" includes the indicated amount ± 10%.

Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may in some cases refer to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

The invention described and claimed herein is not to be limited in scope by the specific preferred embodiments herein disclosed, since these embodiments are intended as illustrations of several aspects of the invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications include the substitution of known equivalents for any aspect of the invention in order to achieve the same result in substantially the same way. Features and characteristics of one embodiment may be combined with features and characteristics of one embodiment, and steps described with respect to one method may be combined with other steps and/or incorporated into other methods described herein. Such modifications are also intended to fall within the scope of the appended claims.

Claims

1. A delivery device for applying adhesive between an anterior mitral leaflet and a posterior mitral leaflet for local fusion thereof, the delivery device comprising:

one or more capture features for capturing the anterior and posterior mitral leaflets;

an applicator configured to apply the adhesive between the captured anterior and posterior mitral leaflets; and

one or more energy elements configured to cure the applied adhesive.

2. The delivery device of claim 1, wherein at least one of the one or more energy elements is configured to deliver Ultraviolet (UV) radiation to cure the applied adhesive.

3. The delivery device of claim 1, wherein at least one of the one or more energy elements is an optical fiber configured to deliver Ultraviolet (UV) radiation out of a distal tip thereof.

4. The delivery device of any preceding claim, wherein the applicator comprises a porous material through which the adhesive is applied.

5. The delivery device of any preceding claim, wherein the adhesive comprises at least one prepolymer and at least one initiator.

6. The delivery device of claim 5, wherein the at least one prepolymer is activated by one or more functional groups that can react to form crosslinks between polymer chains, and wherein the at least one prepolymer is not activated by biological fluids.

7. The delivery device of any of the preceding claims, wherein the one or more capture features comprise a pair of opposing leaflets, each leaflet configured to articulate between an open configuration and a closed configuration to capture one of the anterior or posterior mitral valve leaflets.

8. The delivery device of any one of claims 1-7, wherein the one or more capture features comprise an inflatable balloon, wherein the inflatable balloon captures one of the anterior mitral leaflet or the posterior mitral leaflet.

9. The delivery device of any one of claims 1 to 8, wherein the one or more capture features comprise at least four manipulable clips, wherein at least two clips are configured to capture the anterior mitral leaflet and at least two clips are configured to capture the posterior mitral leaflet.

10. The delivery device of any one of claims 1 to 9, further comprising a capsule comprising a first end, a second end, and sides extending therebetween, wherein the applicator and the one or more energy elements are connected to the first end of the capsule.

11. The delivery device of claim 10, wherein the one or more energy elements substantially surround the applicator.

12. The delivery device of claim 10 or 11, wherein the applicator is at least one of: (i) detachable from the capsule and (ii) configured to retract within an interior cavity of the capsule.

13. The delivery device of any one of claims 10 to 12, wherein the capsule comprises at least one lumen in fluid communication with the applicator, wherein the adhesive is stored in the at least one lumen prior to application between the anterior and posterior mitral leaflets via the applicator.

14. The delivery device of any of claims 10-13, further comprising an arm connected to a second end of the capsule.

15. The delivery device of claim 14, further comprising an expandable stent connected to at least a portion of the capsule or at least a portion of the arm, wherein the expandable stent is configured to stabilize the delivery device during application of the adhesive between the anterior and posterior mitral leaflets.

16. The delivery device of any one of claims 10 to 15, wherein the one or more capture features comprise a pair of opposing leaflets connected to at least a portion of the capsule, wherein each leaflet is configured to articulate between an open configuration and a closed configuration to capture one of an anterior mitral leaflet or a posterior mitral leaflet.

17. The delivery device of any one of claims 10 to 16, wherein the one or more capture features comprise an inflatable balloon, wherein the inflatable balloon captures one of an anterior mitral leaflet or a posterior mitral leaflet.

18. The delivery device of any of claims 10-17, wherein the one or more capture features comprise at least four manipulable clips, wherein at least two clips are configured to capture the anterior mitral leaflet and at least two clips are configured to capture the posterior mitral leaflet.

19. A delivery device for applying an adhesive between natural leaflets for local fusion thereof, the delivery device comprising:

a capture feature for capturing the native leaflet;

an applicator configured to apply the adhesive between each of the native leaflets when captured by the capture feature; and

one or more curing members configured to cure the adhesive after the adhesive is applied to the native leaflets.

20. The delivery device of claim 19, wherein at least one of the one or more curing elements is configured to deliver Ultraviolet (UV) radiation to cure the adhesive.

21. The delivery device of claim 19, wherein at least one of the one or more curing elements is an optical fiber configured to deliver Ultraviolet (UV) radiation out of a distal tip thereof.

22. The delivery device of any one of claims 19-21, wherein the applicator comprises a porous material through which the adhesive is applied.

23. The delivery device of any one of claims 19-22, wherein the adhesive comprises at least one prepolymer and at least one initiator.

24. The delivery device of claim 23, wherein the at least one prepolymer is activated by one or more functional groups that can react to form crosslinks between polymer chains, and wherein the at least one prepolymer is not activated by biological fluids.

25. The delivery device of claim 23 or 24, wherein the at least one initiator is a photoinitiator.

26. The delivery device of any one of claims 19-25, wherein the capture feature comprises opposing leaves, each leaf configured to articulate between an open configuration and a closed configuration to capture one of the native leaflets.

27. The delivery device of any of claims 19-26, wherein the capture feature comprises a balloon, wherein the balloon is inflatable to capture one of the native leaflets.

28. The delivery device of any of claims 19-27, wherein the capture feature comprises at least four manipulable clips, wherein at least two clips are configured to capture a first native leaflet and at least two clips are configured to capture a second native leaflet.

29. The delivery device of any of claims 19-28, further comprising a capsule comprising a first end, a second end, and sides extending therebetween, wherein the applicator and the one or more curing elements are connected to the first end of the capsule.

30. The delivery device of claim 29, wherein the one or more curing elements are spaced apart at equally spaced locations around the applicator.

31. The delivery device of claim 29 or 30, wherein the capsule comprises at least one lumen in fluid communication with the applicator, wherein the adhesive is stored in the at least one lumen prior to application between the native leaflets via the applicator.

32. The delivery device of any of claims 29-31, further comprising an arm connected to a second end of the capsule.

33. The delivery device of claim 32, further comprising an expandable stent coupled to at least a portion of the capsule or at least a portion of the arm, wherein the expandable stent is configured to stabilize the delivery device during application of the adhesive between the native leaflets.

34. The delivery device of any one of claims 19-33, wherein the applicator is configured as at least one of: (i) retracted within the lumen of the delivery device, or (ii) separated from other components of the delivery device.

35. A delivery device for applying adhesive between a native mitral anterior leaflet and a native mitral posterior leaflet for local fusion thereof, the delivery device comprising:

capturing means for capturing the anterior leaflet and the posterior leaflet;

an applicator configured to apply the adhesive between the anterior leaflet and the posterior leaflet once captured by the capture tool; and

at least one curing element configured to cure the adhesive after the adhesive is applied between the anterior leaflet and the posterior leaflet.

36. The delivery device of claim 35, wherein the at least one curing element is configured to deliver Ultraviolet (UV) radiation to cure the adhesive.

37. The delivery device of any one of claims 35 and 36, wherein the adhesive comprises at least one prepolymer and at least one initiator.

38. The delivery device of claim 37, wherein the at least one prepolymer is activated by one or more functional groups that can react to form crosslinks between polymer chains, and wherein the at least one prepolymer is not activated by biological fluids.

39. The delivery device of any one of claims 35-38, wherein the capture means comprises a pair of opposing leaves, each leaf configured to articulate between an open configuration and a closed configuration to capture one of the anterior leaf or the posterior leaf, respectively.

40. The delivery device of any one of claims 35-38, wherein the capture means comprises a pair of inflatable balloons, each inflatable balloon configured to inflate to capture one of the anterior mitral valve leaflet or the posterior mitral valve leaflet, respectively.

41. The delivery device of any of claims 35-38, wherein the capture means comprises a plurality of clips, wherein at least two clips of the plurality of clips are configured to capture the anterior leaflet and at least two clips of the plurality of clips are configured to capture the posterior leaflet.

42. The delivery device of any of claims 35-41, further comprising a capsule comprising a first end, a second end, and sides extending therebetween, wherein the applicator and the at least one curing element are connected to the first end of the capsule.

43. The delivery device of any of claims 35-42, wherein the applicator is configured to retract within another component of the delivery device.

44. The delivery device of any of claims 35-43, further comprising an expandable scaffold, wherein the expandable scaffold is configured to stabilize the delivery device during application of the adhesive between the anterior and posterior leaflets.

45. A delivery device for applying an adhesive between leaflets of a tissue valve for local fusion thereof, the delivery device comprising:

a capture tool for capturing at least a first leaflet and a second leaflet of the tissue valve;

an applicator configured to apply the adhesive between at least the first leaflet and the second leaflet once the first leaflet and the second leaflet are captured by the capture tool; and

at least one energy element configured to cure the adhesive after the adhesive is applied between at least the first leaflet and the second leaflet.

46. The delivery device of claim 45, wherein at least one energy element is configured to deliver Ultraviolet (UV) radiation to cure the adhesive.

47. The delivery device of any one of claims 45 and 46, wherein the adhesive comprises at least one prepolymer and at least one initiator.

48. The delivery device of claim 47, wherein the at least one prepolymer is activated by one or more functional groups that can react to form crosslinks between polymer chains, and wherein the at least one prepolymer is not activated by biological fluids.

49. The delivery device of any one of claims 45-48, wherein the capture tool comprises a pair of opposing leaflets, each leaflet configured to articulate between an open configuration and a closed configuration to capture the first leaflet or the second leaflet, respectively.

50. The delivery device of any one of claims 45-49, wherein the capture tool comprises a pair of balloons, each balloon configured to inflate to capture one of the first leaflet or the second leaflet.

51. The delivery device of any one of claims 45-49, wherein the capture means comprises a plurality of clips, wherein at least two clips of the plurality of clips are configured to capture the first leaflet and at least two clips of the plurality of clips are configured to capture the second leaflet.

52. The delivery device of any of claims 45-51, further comprising a capsule comprising a first end, a second end, and sides extending therebetween, wherein the applicator and the at least one energy element are connected to the first end of the capsule.

53. The delivery device of any one of claims 45-52, wherein the applicator is at least one of: (i) detachable from other components of the delivery device, and (ii) configured to retract within another component of the delivery device.

54. The delivery device of any one of claims 45-53, further comprising an expandable stent, wherein the expandable stent is configured to stabilize the delivery device during application of the adhesive between at least the first leaflet and the second leaflet.

55. A method of locally fusing leaflets of a tissue valve or heart valve via application of an adhesive therebetween, the method comprising:

positioning the delivery device of any of claims 45-54 adjacent to at least a first leaflet and a second leaflet of the tissue valve or heart valve,

capturing the first and second leaflets, respectively, via a capture tool of the delivery device;

applying the adhesive between at least the first leaflet and the second leaflet via an applicator of the delivery device; and

after applying the adhesive, curing the adhesive via at least one energy element of the delivery device to locally fuse at least the first leaflet and the second leaflet together.